Induction of Myeloid-Derived Suppressor Cells in Cryopyrin-Associated Periodic Syndromes.

Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations in the NLRP3 gene leading to overproduction of IL-1ß and other NLRP3 inflammasome products. Myeloid-derived suppressor cells (MDSCs) represent a novel innate immune cell subset capable of suppressing T-cell responses. As inflammasome products were previously found to induce MDSCs, we hypothesized that NLRP3 inflammasome-dependent factors induce the generation of MDSCs in CAPS. We studied neutrophilic MDSCs, their clinical relevance, and MDSC-inducing factors in a unique cohort of CAPS patients under anti-IL-1 therapy. Despite anti-IL-1 therapy and low clinical disease activity, CAPS patients showed significantly elevated MDSCs compared to healthy controls. MDSCs were functionally competent, as they suppressed polyclonal T-cell proliferation, as well as Th1 and Th17 responses. In addition, MDSCs decreased monocytic IL-1ß secretion. Multiplex assays revealed a distinct pattern of MDSC-inducing cytokines, chemokines, and growth factors. Experimental analyses demonstrated that IL-1 cytokine family members and autoinflammation-associated alarmins differentially induced human MDSCs. Increased MDSCs might represent a novel autologous anti-inflammatory mechanism in autoinflammatory conditions and may serve as a future therapeutic target.

Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells.

BACKGROUND: Peripheral homing of progenitor cells in areas of diseased organs is critical for tissue regeneration. The chemokine stromal cell-derived factor-1 (SDF-1) regulates homing of CD34+ stem cells. We evaluated the role of platelet-derived SDF-1 in adhesion and differentiation of human CD34+ cells into endothelial progenitor cells. METHODS AND RESULTS: Adherent platelets express substantial amounts of SDF-1 and recruit CD34+ cells in vitro and in vivo. A monoclonal antibody to SDF-1 or to its counterreceptor, CXCR4, inhibits stem cell adhesion on adherent platelets under high arterial shear in vitro and after carotid ligation in mice, as determined by intravital fluorescence microscopy. Platelets that adhere to human arterial endothelial cells enhance the adhesion of CD34+ cells on endothelium under flow conditions, a process that is inhibited by anti-SDF-1. During intestinal ischemia/reperfusion in mice, anti-SDF-1 and anti-CXCR4, but not isotype control antibodies, abolish the recruitment of CD34+ cells in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet-induced differentiation of CD34+ cells into endothelial progenitor cells, as verified by colony-forming assays in vitro. CONCLUSIONS: These findings imply that platelet-derived SDF-1 regulates adhesion of stem cells in vitro and in vivo and promotes differentiation of CD34+ cells to endothelial progenitor cells. Because tissue regeneration depends on recruitment of progenitor cells to peripheral vasculature and their subsequent differentiation, platelet-derived SDF-1 may contribute to vascular and myocardial regeneration.

["Hospice concerns the whole person!"--voluntary hospice helpers supporting dementia patients]. / "Zu Hospiz gehört doch der ganze Mensch!"--Ehrenamtliche Hospizbegleiter im Einsatz bei Demenzkranken.

Due to demographic change and increase of dementia there is an obvious need of voluntary hospice helpers who support dementia patients. The aim of this qualitative study was to describe the experience and challenges of hospice volunteers supporting dementia patients. The results were taken into account in the development of a training course. Ten narrative interviews were conducted with voluntary hospice helpers. The audiotaped interviews were analysed according to an interpretative phenomenological method. Three main issues, each consisting of three catagories, emerged from the interview data. The voluntary hospice helpers experience different facets and the progress of dementia ("to experience the process"). They provide a pleasant change in everyday life of and express their solidarity with dementia patients ("to create a good atmosphere"). They empathetically support dementia patients without expecting anything in return and they benefit from their work with dying people ("to put one's own interests last"). Voluntary hospice helpers offer important support for dementia patients but their role in the interdisciplinary team has to be defined. Training courses are useful to improve interaction and reflection skills.

["Quality of life means acting independently". How do COPD-patients experience non-invasive ventilation? A qualitative study]. / "Für mich ist Lebensqualität, selbständig handeln zu können..." Wie erleben COPD-Patienten ihre Heimbeatmung? Eine qualitative Studie.

Chronic obstructive pulmonary disease (COPD) is a progressive disorder including chronic obstructive bronchitis, emphysema and combinations. The management of stable COPD in an advanced stage involves noninvasive mechanical ventilation. There is a lack of convincing scientific studies about the influence of mechanical ventilation on quality of life. Furthermore the role of nurses taking care of people with COPD seems to be unclear. A phenomenological interpretative-hermeneutical analysis of 15 narrative interviews with non-invasive ventilated COPD-patients demonstrates that noninvasive ventilation is associated with improvements in patients' autonomy. "To achieve independence" is described as the central theme of this study and highlights the benefit of independency on patients' quality of life. Other results describe the experiences "To experience breathing", "To seize one's possibilities", "To participate in life", "To have to live with COPD". The results also show that activities of nurses in particular need to include consulting, teaching and monitoring. There is a need for further research to evaluate nursing interventions. This study is a first step in knowledge generation and serves as a basis for further quantitative research.

Fondaparinux and enoxaparin in comparison to unfractionated heparin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model.

The aim of the present study was to investigate the efficacy of three different parenterally administered anticoagulants for the prevention of thrombus formation on artificial heart valves in an experimental rabbit model. Unfractionated heparin was administered intravenously in group I (n = 10), Enoxaparin subcutaneously in group II (n = 10), fondaparinux intravenously in group III (n = 10), and no medication was administered to group IV (n = 9). Leaflets from Sulzer Carbomedics bileaflet mechanical heart valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein. In group IV the flow chamber was clotted after a median of 15 minutes of circulation. Weight analysis before and after 1 h of perfusion showed that the median thrombus weight was 18.0 mg in group I, 17.7 mg in group II, 20.3 mg in group III, and 30.8 mg in group IV. Further analysis by electron microscopy showed similar results regarding deposition of fibrin, platelets, and erythrocytes on leaflet surfaces. Fondaparinux and subcutaneously administered enoxaparin were as effective as intravenously administered unfractionated heparin in preventing thrombus formation on artificial heart valve leaflets in our investigation. This rabbit model, in which the heart valve leaflets were exposed to rabbit blood for a short time under laminar flow, should be further evaluated with respect to whether it can provide information about anti-thrombotic regimens in patients after mechanical heart valve replacement.